Celastrol attenuates atherosclerosis in Apolipoprotein E (apoE) knockout mice fed an atherogenic diet

The study is aimed to investigate the effects of celastrol on the atherogenesis in apolipoprotein E knockout (apoE-/-) mice fed an atherogenic diet. All mice were fed a high-fat and high-cholesterol diet for 8 weeks. In the last 4 weeks, apoE-/- mice were randomly grouped to receive treatment with either celastrol (2 mg/kg/day in DMSO, i.p.) or vehicle DMSO (n=6 per group). Plasma lipids were determined enzymatically. The area of atherosclerotic lesions was measured by hematoxylin and eosin staining. The expression of macrophage migration inhibitory factor (MIF), matrix metalloproteinase-9 (MMP-9), CD40 ligand (CD40L) and C-reactive protein (CRP) were assayed by immunohistochemistry. Celastrol inhibited the development of atherosclerotic lesions in apoE-/- mice. The expressions of MIF, MMP-9, CD40L and CRP in the artery wall were significantly reduced by celastrol. Meanwhile, the lipid profile in the mice was not improved. In conclusion, our study demonstrates that celastrol inhibits atherogenesis in celastrol-treated apoE-/- mice fed an atherogenic diet by inhibiting inflammation in the arterial wall without improving the lipid profile.   Key words: Celastrol, atherosclerosis, CD40 ligand, macrophage migration inhibitory factor,matrix metalloproteinase-9.